Journal of the National Cancer Institute · 2025
Dynamic ctDNA informs whole-course postoperative precise management of NSCLC (LUNGCA study).
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Xia Liang, Pu Qiang, Kang Ran, Mei Jiandong, Li Lu, Yang Ying, Deng Senyi, Feng Gang, Deng Yulan, Gan Fanyi, Lin Yidan, Ma Lin, Lin Feng, Yuan Yong, Hu Yang, Guo Chenglin, Liao Hu, Liu Chengwu, Zhu Yunke, Wang Wenping, Liu Zheng, Xu Yuyang, Li Kaidi, Li Chuan, Chen Weizhi, Li Qingyun, Du Bo, Zhang Xiaolong, Kou Yingli, Wang Yun, Wu Zhu, Che Guowei, Chen Yaohui, Shen Shensi, Chen Longqi, Xie Dan, Liu Lunxu
Аннотация
BACKGROUND: Circulating tumor DNA (ctDNA) is valuable for detecting minimal residual disease (MRD). However, studies involving long-term blood sampling are required to comprehensively interpret the clinical use of ctDNA analyses.
METHODS: We conducted a prospective multicenter cohort study (LUNGCA) for dynamic ctDNA monitoring in lung cancer patients receiving curative-intent surgery. ctDNA analysis was conducted on preoperative plasma samples, at postoperative 3 days and 1 month, and then every 3-6 months for up to 3 years.
RESULTS: In total, 233 non-small cell lung cancer (NSCLC) patients and 2336 longitudinal plasma samples were included; the median follow-up was 51.4 months. Post-comprehensive treatment (after radical surgery + necessary adjuvant therapy) MRD status was better at predicting relapse than postoperative MRD status (positive predictive value: 100% vs 90.0%; negative predictive value: 90.3% vs 90.1%). Patients with positive pre-adjuvant ctDNA and targetable mutations in tumor tissues had improved recurrence-free survival (RFS) with corresponding adjuvant tyrosine kinase inhibitor (TKI) treatment (hazard ratio [HR] = 0.01, P = .005), but adjuvant chemotherapy failed to improve RFS (HR = 0.6, P = .491). Of patients receiving adjuvant therapies, patients with a negative- or positive-negative ctDNA change pattern had favorable and similar RFS (P = .419), whereas patients with a positive- or negative-positive pattern had worse RFS (P < .001). TKI therapy was more effective than chemotherapy in clearing ctDNA. Post-relapse ctDNA negativity was associated with favorable OS (HR = 0.4; P = .029).
CONCLUSIONS: Comprehensive interpretation of dynamic ctDNA monitoring data can inform precise whole-course postsurgical management of NSCLC patients.
METHODS: We conducted a prospective multicenter cohort study (LUNGCA) for dynamic ctDNA monitoring in lung cancer patients receiving curative-intent surgery. ctDNA analysis was conducted on preoperative plasma samples, at postoperative 3 days and 1 month, and then every 3-6 months for up to 3 years.
RESULTS: In total, 233 non-small cell lung cancer (NSCLC) patients and 2336 longitudinal plasma samples were included; the median follow-up was 51.4 months. Post-comprehensive treatment (after radical surgery + necessary adjuvant therapy) MRD status was better at predicting relapse than postoperative MRD status (positive predictive value: 100% vs 90.0%; negative predictive value: 90.3% vs 90.1%). Patients with positive pre-adjuvant ctDNA and targetable mutations in tumor tissues had improved recurrence-free survival (RFS) with corresponding adjuvant tyrosine kinase inhibitor (TKI) treatment (hazard ratio [HR] = 0.01, P = .005), but adjuvant chemotherapy failed to improve RFS (HR = 0.6, P = .491). Of patients receiving adjuvant therapies, patients with a negative- or positive-negative ctDNA change pattern had favorable and similar RFS (P = .419), whereas patients with a positive- or negative-positive pattern had worse RFS (P < .001). TKI therapy was more effective than chemotherapy in clearing ctDNA. Post-relapse ctDNA negativity was associated with favorable OS (HR = 0.4; P = .029).
CONCLUSIONS: Comprehensive interpretation of dynamic ctDNA monitoring data can inform precise whole-course postsurgical management of NSCLC patients.